The congestive heart failure state is characterized by elevated sympathetic tone and depressed cardiac vagal tone. In addition to the increased sympathetic outflow, vasopressin, renin, angiotensin II, and aldosterone are all elevated in congestive heart failure. The mechanism(s) responsible for this neurohumoral activation are not well understood. It has been reported that the sustained increase in neurohumoral drive in chronic congestive heart failure is mediated by the blunted arterial baroreceptor and cardiopulmonary receptor reflexes. In addition to cardiopulmonary vagal reflexes , it is well known that cardiac "sympathetic afferent" reflexes contribute to increases in sympathetic outflow and are stimulated by a variety of endogenous substances. This mechanism if, of course, a positive feedback mechanism and can only be deleterious to the organism over the long term. Because the heart is dilated, hypertrophied and faced with a reduction in coronary perfusion pressure in heart failure, myocardial oxygen consumption is elevated in this disease state. While this could act as a mechanism by which sympathetic afferents are stimulated, little is known concerning their role in regulating sympathetic outflow in heart failure. It is possible that cardiac sympathetic afferents may be sensitized or overtly stimulated in heart failure and contribute to the sustained sympathetic drive in this disease state. Therefore, the specific aims of this grant proposal are; 1). To determine differences of cardiac sympathetic afferent reflexes between normal dogs and dogs with experimental heart failure; 2). To determine if enhanced angiotensin converting enzyme (ACE) activity plays an important role in the abnormal cardiac sympathetic afferent reflex in heart failure; 3). To determine if prostaglandins are involved in mediating the abnormal cardiac sympathetic afferent reflex in heart failure; 4) To determine the electrophysiological characteristics of cardiac sympathetic afferent receptors in heart failure; 5). To determine if there is an abnormality in the central processing of the cardiac sympathetic afferent reflex control of sympathetic outflow in heart failure. These studies will be carried out using techniques for the evaluation of hemodynamics in conscious dogs with and without heart failure and using anesthetized preparations for electrophysiological experiments. These studies will extend our understanding of the regulation of sympathetic tone in heart failure. In addition, the data acquired may provide important new information concerning the role of cardiac sympathetic afferent reflexes in the neural control of the circulation.